Review of duloxetine in the management of diabetic peripheral neuropathic pain.

Smith T, Nicholson RA - Vasc Health Risk Manag (2007)

Bottom Line:
This compound has no other significant receptor or channel activities other than the serotonin and norepinephrine reuptake inhibition mechanisms and works to diminish or control the symptoms of diabetic neuropathy.Duloxetine has no known neuroprotective or other effects which prevent the development of neuropathy in patients with diabetes.These findings provide support for the proposed role of serotonin and norepinephrine as key mediators of the descending pain inhibition pathways of the brain stem and spinal cord.

ABSTRACTDuloxetine is a balanced selective serotonin norepinephrine reuptake inhibitor (SNRI) which, in 2004, became the first agent to receive regulatory approval for the treatment of painful diabetic neuropathy in the US. This compound has no other significant receptor or channel activities other than the serotonin and norepinephrine reuptake inhibition mechanisms and works to diminish or control the symptoms of diabetic neuropathy. Duloxetine has no known neuroprotective or other effects which prevent the development of neuropathy in patients with diabetes. The purpose of this review article is to discuss the background of painful diabetic neuropathy, the pharmacology of duloxetine, and its safety and efficacy in clinical trials and long-term observations. The authors will also comment on its use in clinical practice. Results from controlled clinical trials reveal that duloxetine administered at 60 mg qd or 60 mg bid is efficacious in treating diabetic neuropathic pain relative to placebo. Positive treatment outcomes are also seen for other measures of pain and quality of life. A minor but statistically significant increase in blood glucose compared with placebo treated patients has been observed in controlled clinical trials. Otherwise, controlled and open-label clinical studies have demonstrated a high degree of safety and tolerability for the compound. These findings provide support for the proposed role of serotonin and norepinephrine as key mediators of the descending pain inhibition pathways of the brain stem and spinal cord.

Mentions:
Safety and tolerability was evaluated for all three controlled trials as well as three long term (52 week) open label studies (Raskin et al 2006; Wernicke et al 2006a, b, 2007). We will first report the safety and tolerability findings of the blinded trials. Overall, 67/339 (19.7%) discontinued during the study period. Figure 5 shows the pooled percentage that discontinued from each arm among the controlled trials (Goldstein et al 2005; Raskin et al 2005; Wernicke et al 2006a, b). In regards to serious adverse events (SAEs), a total of 41/1139 (3.6%) patients reported at least one SAE; however, SAEs did not differ among groups. Goldstein et al (2005) and Wernicke et al (2006a, b) included the treatment emergent adverse events (TEAEs) for each group as well as lipid profiles. Figure 6 shows the percentages of individuals who experienced the most common TEAEs. Table 4 shows the pooled changes in lipid profiles and glycosylated hemoglobin (HbA1c). The only group difference was for high density lipoprotein (HDL) between the duloxetine 60 mg bid and placebo treatment arms; however, the difference (0.027) is not clinically significant.

Mentions:
Safety and tolerability was evaluated for all three controlled trials as well as three long term (52 week) open label studies (Raskin et al 2006; Wernicke et al 2006a, b, 2007). We will first report the safety and tolerability findings of the blinded trials. Overall, 67/339 (19.7%) discontinued during the study period. Figure 5 shows the pooled percentage that discontinued from each arm among the controlled trials (Goldstein et al 2005; Raskin et al 2005; Wernicke et al 2006a, b). In regards to serious adverse events (SAEs), a total of 41/1139 (3.6%) patients reported at least one SAE; however, SAEs did not differ among groups. Goldstein et al (2005) and Wernicke et al (2006a, b) included the treatment emergent adverse events (TEAEs) for each group as well as lipid profiles. Figure 6 shows the percentages of individuals who experienced the most common TEAEs. Table 4 shows the pooled changes in lipid profiles and glycosylated hemoglobin (HbA1c). The only group difference was for high density lipoprotein (HDL) between the duloxetine 60 mg bid and placebo treatment arms; however, the difference (0.027) is not clinically significant.

Bottom Line:
This compound has no other significant receptor or channel activities other than the serotonin and norepinephrine reuptake inhibition mechanisms and works to diminish or control the symptoms of diabetic neuropathy.Duloxetine has no known neuroprotective or other effects which prevent the development of neuropathy in patients with diabetes.These findings provide support for the proposed role of serotonin and norepinephrine as key mediators of the descending pain inhibition pathways of the brain stem and spinal cord.

ABSTRACTDuloxetine is a balanced selective serotonin norepinephrine reuptake inhibitor (SNRI) which, in 2004, became the first agent to receive regulatory approval for the treatment of painful diabetic neuropathy in the US. This compound has no other significant receptor or channel activities other than the serotonin and norepinephrine reuptake inhibition mechanisms and works to diminish or control the symptoms of diabetic neuropathy. Duloxetine has no known neuroprotective or other effects which prevent the development of neuropathy in patients with diabetes. The purpose of this review article is to discuss the background of painful diabetic neuropathy, the pharmacology of duloxetine, and its safety and efficacy in clinical trials and long-term observations. The authors will also comment on its use in clinical practice. Results from controlled clinical trials reveal that duloxetine administered at 60 mg qd or 60 mg bid is efficacious in treating diabetic neuropathic pain relative to placebo. Positive treatment outcomes are also seen for other measures of pain and quality of life. A minor but statistically significant increase in blood glucose compared with placebo treated patients has been observed in controlled clinical trials. Otherwise, controlled and open-label clinical studies have demonstrated a high degree of safety and tolerability for the compound. These findings provide support for the proposed role of serotonin and norepinephrine as key mediators of the descending pain inhibition pathways of the brain stem and spinal cord.